Compositions and delivery methods for treating dental infections, inflammation, sensitivity, and for use in dental restorations

Abstract

The present invention provides a method of treating a condition affecting a tooth or periodontium in a subject, comprising administering to the subject's tooth or periodontium a composition comprising biocompatible magnetic, magnetizable, or magnetically responsive agents; and applying an external magnetic field, wherein the magnetic, magnetizable, or magnetically responsive agents migrate to a desired location in response to the externally applied magnetic field, thereby treating a condition affecting the tooth or periodontium in the subject.

What is claimed is: 
     
       1. A method of treating a condition affecting a tooth or periodontium in a subject, comprising:
 i) administering to the subject's tooth or periodontium a composition comprising biocompatible magnetic, magnetizable, or magnetically responsive agents; and 
 ii) applying an external magnetic field; 
 
       wherein the magnetic, magnetizable, or magnetically responsive agents migrate to a desired location through dentinal tubules in response to the externally applied magnetic field, thereby treating a condition affecting the tooth or periodontium in the subject, wherein the magnetic, magnetizable, or magnetically responsive agents comprise particles, fluids, rods, cubes, or agents of other shape, wherein the magnetic, magnetizable, or magnetically responsive agents do not comprise liposomes; and 
       wherein the affected tooth or a tooth adjacent to the affected periodontium has a pulp chamber, wherein the affected tooth or the tooth adjacent to the affected periodontium comprises a hard tissue that surrounds a pulp chamber, wherein the hard tissue comprises dentin and/or enamel, wherein if dentin is not exposed, the method further comprises excising hard tissue to expose dentin, wherein any excising of the hard tissue does not affect the integrity of the pulp chamber by exposing pulp. 
     
     
       2. The method of  claim 1 , wherein the composition comprises an effective amount of one or more therapeutic agents. 
     
     
       3. The method of  claim 2 , wherein the therapeutic agent is bound to the magnetic, magnetizable, or magnetically responsive agents chemically, ionically, covalently, non-covalently, using a thin film rehydration method, by dialysis, by mechanical absorption polymerization or a combination thereof. 
     
     
       4. The method of  claim 2 , wherein the therapeutic agent is selected from the group consisting of a remineralizing agent, a restorative/bonding material, an anti-inflammatory agent, an immunosuppressant, an analgesic, an antibody, an antibiotic, an antibacterial, an anti-fungal, a dental anesthetic, a desensitizing agent, recombinant RNA, recombinant DNA, lipopolysaccharides, a therapeutic protein, and combinations thereof. 
     
     
       5. The method of  claim 2 , wherein the composition comprises a desensitizing agent selected from the group consisting of glutaraldehyde, silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, strontium chloride, potassium oxalate, calcium phosphate, calcium carbonate, bio active glasses (e.g., SiO2—P2O5—CaO—Na2O), fluoride varnishes, oxalic acid and resin, glass ionomer cements, composites, dentin bonding agents, propolis and combinations thereof. 
     
     
       6. The method of  claim 2 , wherein the composition comprises an antibiotic selected from the group consisting of tetracycline, demeclocycline, doxycycline, minocycline, lymecycline, oxytetracycline, triclosan, penicillin, penicilline V, phenoxymethylpenicillin, flucloxacillin, amoxicillin, cephalosporins, cefaclor, cefadroxil, cephalexin, aminoglycoside, gentamicin, tobramycin, macrolide, erythromycin, azithromycin, clarithromycin, clindamycin, vancomycin, sulfonamide, trimethoprim, co-trimoxazole, metronidazole, tinidazole, quinolone, ciprofloxacin, levofloxacin, norfloxacin, ofloxacine and combinations thereof. 
     
     
       7. The method of  claim 2 , wherein the composition comprises an anti-inflammatory agent selected from the group consisting of a non-steroidal anti-inflammatory agent, a corticosteroid, aspirin, celecoxib, diclofenac, diflunisal, etodolac, ibuprofen, indomethacin, ketoprofen, ketorolac, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, tolmetin, hydrocortisone, cortisone, ethamethasoneb, prednisone, prednisolone, triamcinolone, methylprednisolone, aldosterone, betamethasone, dexamethasone, mineralocorticoid, fludrocortisone and combinations thereof. 
     
     
       8. The method of  claim 2 , wherein the composition comprises an analgesic agent selected from the group consisting of opioids, codeine, fentanyl, hydrocodone, hydromorphone, propofol, meperidine, methadone, morphine, oxycodone, non-opioids, tramadol and combinations thereof. 
     
     
       9. The method of  claim 2 , wherein the composition comprises an anesthetic selected from the group consisting of benzocaine, chloroprocaine, cocaine, cyclomethycaine, dimethocaine/larocaine, piperocaine, propoxycaine, procaine/novocaine, proparacaine, tetracaine/amethocaine, articaine, bupivacaine, cinchocaine/dibucaine, etidocaine, levobupivacaine, lidocaine/lignocaine, mepivacaine, prilocaine, ropivacaine, trimecaine, saxitoxin, neosaxitoxin, tetrodotoxin, menthol, eugenol and combinations thereof. 
     
     
       10. The method of  claim 2 , wherein the composition comprises an anti-fungal agent selected from the group consisting of nystatin, amphotericin B, ketoconazole, miconazole and combinations thereof. 
     
     
       11. The method of  claim 2 , wherein the composition comprises chlorhexidine as an antibacterial agent. 
     
     
       12. The method of  claim 1 , wherein the condition affecting the tooth or periodontium is selected from the group consisting of inflammation, pulpitis, infection, pain, sensitivity, caries (tooth decay), structural loss, gingivitis, periodontitis, periodontal disease, pericoronitis, and osteoradionecrosis, medication induced necrosis of the bone, degeneration, atrophy, abscess, and resorption. 
     
     
       13. The method of  claim 1 , wherein the agents have a size of from 1 nm to 2.0 μm. 
     
     
       14. The method of  claim 1 , wherein the magnetic, magnetizable, or magnetically responsive agents are paramagnetic, superparamagnetic materials, ferromagnetic or ferrimagnetic materials. 
     
     
       15. The method of  claim 1 , wherein the magnetic, magnetizable, or magnetically responsive agents are nanoparticles and comprise an iron core. 
     
     
       16. The method of  claim 15 , wherein the nanoparticles are superparamagnetic iron oxide nanoparticles. 
     
     
       17. The method of  claim 1 , wherein the magnetic, magnetizable, or magnetically responsive agents have a size of from 50 nm to 1500 nm. 
     
     
       18. The method of  claim 1 , wherein the magnetic, magnetizable, or magnetically responsive agents comprise a magnetic, magnetizable, or magnetically responsive core coated with a shell comprising a biocompatible polymer or polysaccharide matrix. 
     
     
       19. The method of  claim 18 , wherein the core is coated with a biocompatible polymer. 
     
     
       20. The method of  claim 19 , wherein the composition comprises an effective amount of a therapeutic agent, wherein the therapeutic agent is within the shell and the release of the therapeutic agent is sustained over a period of time. 
     
     
       21. The method of  claim 1 , wherein the external magnetic field has a strength of about 0.1 to about 3.0 Tesla. 
     
     
       22. The method of  claim 1 , wherein the composition comprises effective amounts of one or more of the following: hydroxyapatite, calcium titanate, potassium chloride, ceramics, Bis-GMA/dental adhesives, zinc, silver, gold, capsaicin, or amelogenin. 
     
     
       23. The method of  claim 1 , wherein the composition is applied to a cavity. 
     
     
       24. The method of  claim 1 , wherein the composition is applied to a surface of dentin. 
     
     
       25. The method of  claim 1 , wherein the composition is applied to a periodontal pocket. 
     
     
       26. The method of  claim 1 , wherein the condition is pulpitis. 
     
     
       27. The method of  claim 1 , wherein the condition is caries (tooth decay). 
     
     
       28. The method of  claim 1 , wherein the externally applied magnetic field is applied for about 30 seconds to about 60 minutes. 
     
     
       29. The method of  claim 1 , wherein the external magnetic field is provided by one or more neodymium magnets. 
     
     
       30. The method of  claim 1 , wherein the magnetic field is optimized using finite element analysis and magnetic modeling to optimize magnet placement, so as to have a steep, uniform magnetic gradient over a specific region in space corresponding to a region of interest in the tooth or periodontium. 
     
     
       31. The method of  claim 1 , wherein one or more magnets are positioned inside the oral cavity. 
     
     
       32. The method of  claim 1 , wherein one or more magnets are positioned outside the oral cavity. 
     
     
       33. The method of  claim 1 , wherein one or more magnets are held into position using a mouthpiece. 
     
     
       34. The method of  claim 33 , wherein one or more magnets are placed underneath the jaw to direct the magnetic, magnetizable, or magnetically responsive agents into the pulp of the lower teeth. 
     
     
       35. A dental delivery system for delivering one or more therapeutically effective agents to a desired location in a subject's tooth or periodontium comprising:
 i) one or more magnets capable of applying an external magnetic field; and 
 ii) a composition comprising biocompatible magnetic, magnetizable, or magnetically responsive agents; wherein the magnetic, magnetizable, or magnetically responsive agents migrate to a desired location in dentinal tubules in response to the externally applied magnetic field, wherein the magnetic, magnetizable, or magnetically responsive agents comprise particles, fluids, rods, cubes, or agents of other shape, wherein the magnetic, magnetizable, or magnetically responsive agents do not comprise liposomes; and 
 
       wherein the affected tooth or a tooth adjacent to the affected periodontium has a pulp chamber, wherein the affected tooth or the tooth adjacent to the affected periodontium comprises a hard tissue that surrounds a pulp chamber, wherein the hard tissue comprises dentin and/or enamel, wherein the system allows migration of the magnetic, magnetizable, or magnetically responsive agents without the necessity of excising hard tissue in order to expose pulp of the pulp chamber. 
     
     
       36. The system of  claim 35 , wherein the composition comprises an effective amount of one or more therapeutic agents. 
     
     
       37. The system of  claim 35 , wherein the condition affecting the tooth or periodontium is selected from the group consisting of inflammation, pulpitis, infection, pain, sensitivity, caries (tooth decay), structural loss, gingivitis, periodontitis, periodontal disease, pericoronitis, and osteoradionecrosis, medication induced necrosis of the bone, degeneration, atrophy, abscess, and resorption. 
     
     
       38. The method of  claim 1 , wherein the magnetic, magnetizable, or magnetically responsive agents are large enough to experience significant magnetic forces under an applied magnetic field, but small enough to be able to transport through tooth dentin tubules or periodontium.